title: KP-1 is a marker for extraneuronal neurofibrillary tangles and senile plaques in Alzheimer diseased brains.
abstract: KP-1 immunostaining with microwave pretreatment in formalin-fixed, paraffin-embedded sections enhanced its immunoreactivity revealing extraneuronal neurofibrillary tangles (NFTs) called ghost tangles, senile plaques (SPs) and perivascular deposits as well as microglial labelling in Alzheimer-diseased brains. KP-1 stained cored and uncored SPs, granules within the SPs, perivascular beta-amyloid protein (beta AP) and star-like beta AP deposits in cortical layer I, which was confirmed in comparison to silver-impregnated structures in the Reusche-stained or Gallyas-Schiff-stained sections. On double immunostaining with KP-1 and ubiquitin, ghost tangles were labelled by KP-1 and intraneuronal NFTs were positive for ubiquitin. A few KP-1-positive granules deposits different from amyloid core were found within the SPs and the outer margin of amyloid cores of SPs were stained by KP-1. KP-1-positive microglia were attached to the ubiquitin-positive intraneuronal NFTs. Microglia were more numerously labelled by CR3/43 than by KP-1, and CR3/43-positive microglia were found to be preferentially attached to SPs. As KP-1 recognizes lysosome-associated antigen CD68, similarities between KP-1 positivity and Reusche-stained structures suggested that lysosomal activity was associated with beta AP deposits and ghost tangles were involved in lysosome-associated processes. It is speculated that lysosomes play a role in the process of ghost tangle formation and in beta AP deposits leading to SP formation.
authors.affiliation: Department of Neuropsychiatry, Kanazawa University School of Medicine, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: F
authors.initials: F
authors.lastname: Muramori
authors.forename: T
authors.initials: T
authors.lastname: Aoki
authors.forename: M
authors.initials: M
authors.lastname: Hayashi
authors.forename: K
authors.initials: K
authors.lastname: Miyazu
authors.forename: Y
authors.initials: Y
authors.lastname: Fukutani
authors.forename: M
authors.initials: M
authors.lastname: Mukai
authors.forename: F
authors.initials: F
authors.lastname: Koshino
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D000682:Amyloid / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000378:metabolism; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000378:metabolism*; D016707:Tissue Fixation; D014452:Ubiquitins / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D000682:Amyloid; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D014452:Ubiquitins; C067980:CD68 antigen, human; D000097382:CD68 Molecule